A Study to Evaluate the Safety and Efficacy of Itacitinib in Moderate to Severe Ulcerative Colitis

Moderate to Severe Ulcerative Colitis Clinical Trial

Official title:

A Phase 2, Double-Blind, Dose-Ranging, Placebo-Controlled Study With Open-Label Extension to Evaluate the Safety and Efficacy of Itacitinib in Moderate to Severe Ulcerative Colitis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03627052
• Other study ID #: INCB 39110-210
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 20, 2018
• Est. completion date: November 13, 2019

Study information

• Verified date: December 2019
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of itacitinib in participants with moderate to severe ulcerative colitis (UC).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 13, 2019
• Est. primary completion date: November 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of UC at least 12 weeks before screening based on clinical, endoscopic, and histopathological evidence.

• Have a 3-component Mayo score of 4 to 9, which includes a modified Mayo Endoscopy Score (mMES) of = 2 as determined by a central reader, a rectal bleeding score of = 1, and a stool frequency score of = 1.

• Must have failed or be intolerant to (discontinued the medication due to an adverse event as determined by the investigator) at least 1 of the following treatments for UC: Oral corticosteroids, azathioprine or 6-mercaptopurine, biologic therapy (eg, infliximab, vedolizumab or adalimumab).

• Participants currently receiving the following treatment(s) for UC are eligible, provided they have been receiving acceptable and stable dose(s): oral 5-ASA or oral corticosteroids.

• No evidence of active or latent or inadequately treated tuberculosis infection.

• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Clinical signs of fulminant colitis or toxic megacolon.

• Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical or radiographic findings suggestive of Crohn's disease.

• Disease limited to the distal 15 cm of the colon.

• Receiving (or expected to receive) the following therapies within protocol-designated timeframes before the baseline visit or during the study: Natalizumab; anti-TNF therapy; Vedolizumab or any investigational anti-adhesion molecule therapy; Ustekinumab or any on or off label biologic therapy; interferon therapy; cyclosporine, mycophenolate, or tacrolimus; daily dose of oral corticosteroids = 25 mg prednisone or equivalent; intravenous corticosteroids; rectally administered formulation of corticosteroids or 5-aminosalicylic acid; and AZA, 6-MP, or methotrexate.

• Enema treatments within 2 weeks of the baseline visit, with the exception of enema bowel preparations for clinical assessments.

• Positive stool examinations for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin at the screening visit.

• Other immunocompromised states and history of opportunistic infections.

• History of stomach or intestinal surgery, including bariatric surgery (Note:

appendectomy and/or cholecystectomy, is allowed).

o surgery for UC or likely to require surgery for UC during the study.

• If at risk for colorectal cancer, must have had a colonoscopy within protocol-defined timeframes.

• History of recurrent, disseminated, or multiple dermatomal herpes zoster.

• History of alcohol or drug abuse.

• History of active malignancy within 5 years of screening, excluding superficial basal and squamous cell carcinoma of the skin and adequately treated carcinoma in situ of the cervix.

• Current or recent history (within 30 days before randomization) of a clinically meaningful viral, bacterial, fungal, parasitic, or mycobacterial infection.

• Previously received either lymphocyte apheresis or selective monocyte granulocyte apheresis (eg, Cellsorba) within 1 year of baseline.

• History of unstable ischemic heart disease or uncontrolled hypertension.

• Positive serology test results for HIV, for hepatitis B surface antigen or core antibody, or for HCV antibody with detectable RNA at screening.

• Participants taking potent systemic CYP3A4 inhibitors or inducers or fluconazole within 2 weeks or 5 half-lives (whichever is longer) of baseline.

• Participants taking P-gp substrates with narrow therapeutic index, including digoxin within 2 weeks or 5 half-lives (whichever is longer) of baseline.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Moderate to Severe Ulcerative Colitis
• Ulcer

Intervention

Drug:
• Itacitinib
In the double-blind period, itacitinib administered orally once or twice daily at the protocol-defined dose according to treatment group randomization. In the open-label extension, itacitinib administered at doses determined from the double-blind period.
• Placebo
Placebo administered orally twice daily in the double-blind period.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with a Clinical Response	To evaluate the efficacy of itacitinib inducing a Clinical Response.	Week 8
Secondary	Proportion of participants with Endoscopic Response	To evaluate the efficacy of itacitinib on endoscopic outcomes.	Week 8
Secondary	Proportion of participants with Mucosal Healing	To evaluate the efficacy of itacitinib on endoscopic outcomes.	Week 8
Secondary	Proportion of participants in Endoscopic Remission	To evaluate the efficacy of itacitinib on endoscopic outcomes.	Week 8
Secondary	Proportion of participants in Clinical Remission	To evaluate the efficacy of itacitinib on clinical outcomes.	Week 8
Secondary	Change from baseline in 3-component Mayo score	To evaluate the efficacy of itacitinib on clinical outcomes.	Week 8
Secondary	Change from baseline in Physician's Global Assessment score	To evaluate the efficacy of itacitinib on clinical outcomes.	Week 8
Secondary	Change in Quality of Life score as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ)	To evaluate the efficacy of itacitinib on quality of life outcomes.	Week 8
Secondary	Cmax of itacitinib	Maximum observed plasma concentrations.	Week 4
Secondary	Ctau of itacitinib	Plasma concentrations	Weeks 2 and 4
Secondary	Stool concentration of itacitinib -~30-hr collection		Week 4
Secondary	Number of treatment-emergent adverse events	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to approximately 60 weeks